tbuckley/cabot-search huggingface dataset:
Definition and Prognostic Value of Ph-like and IKZF1plus Status in Children With Down Syndrome and B-cell Precursor Acute Lymphoblastic Leukemia
Authors: Chiara Palmi, Silvia Bresolin, Stefanie Junk, Grazia Fazio, Daniela Silvestri, Marketa Zaliova, Athanasios Oikonomou, Katerina Scharov, Martin Stanulla, Anja Moericke, Martin Zimmermann, Martin Schrappe, Barbara Buldini, Sanil Bhatia, Arndt Borkhardt, Claudia Saitta, Marta Galbiati, Michela Bardini, Luca Lo Nigro, Valentino Conter, Maria Grazia Valsecchi, Andrea Biondi, Geertruy te Kronnie, Gunnar Cario, Giovanni Cazzaniga
Journal: HemaSphere (2023)

Children with Down syndrome have an augmented risk for B-cell acute lymphoblastic leukemia (DS-ALL), which is associated with lower survival than in non-DS-ALL. It is known that cytogenetic abnormalities common in childhood ALL are less frequent in DS-ALL, while other genetic aberrancies (ie, CRLF2 overexpression and IKZF1 deletions) are increased. A possible cause for the lower survival of DS-ALL that we herewith evaluated for the first time was the incidence and prognostic value of the Philadelphia-like (Ph-like) profile and the IKZF1plus pattern. These features have been associated with poor outcome in non-DS ALL and therefore introduced in current therapeutic protocols. Forty-six out of 70 DS-ALL patients treated in Italy from 2000 to 2014 displayed Ph-like signature, mostly characterized by CRLF2 (n = 33) and IKZF1 (n = 16) alterations; only 2 cases were positive for ABL -class or PAX5 -fusion genes. Moreover, in an Italian and German joint cohort of 134 DS-ALL patients, we observed 18% patients positive for IKZF1plus feature. Ph-like signature and IKZF1 deletion were associated with poor outcome (cumulative incidence of relapse: 27.7 ± 6.8% versus 13 ± 7%; P = 0.04 and 35.2 ± 8.6% versus 17 ± 3.9%; P = 0.007, respectively), which further worsens when IKZF1 deletion was co-occurring with P2RY8::CRLF2 , qualifying for the IKZF1plus definition (13/15 patients had an event of relapse or treatment-related death). Notably, ex vivo drug screening revealed sensitivity of IKZF1plus blasts for drugs active against Ph-like ALL such as Birinapant and histone deacetylase inhibitors. We provided data in a large setting of a rare condition (DS-ALL) supporting that these patients, not associated with other high-risk features, need tailored therapeutic strategies.
Usefulness of water pressure observation in detection and direct clipping of source of colonic diverticular bleeding
Authors: Jun Takada, Masamichi Arao, Kentaro Kojima, Sachiyo Onishi, Masaya Kubota, Takashi Ibuka, Masahito Shimizu
Journal: Endoscopy (2023)

Colonic diverticular bleeding is the most common cause of bleeding in the lower gastrointestinal tract [1]. Endoscopic identification of stigmata of recent hemorrhage (SRH), such as active bleeding, adherent clot, or visible vessel, is important but often difficult [2] [3]. The waterjet scope, the use of which has been reported to be an independent predictive factor for identifying SRH, is primarily used to wash away feces or clots inside the diverticulum [4]. Herein, we describe a useful case of water pressure observation for the detection of SRH and endoscopic direct clipping of diverticular bleeding.
A simple replacement method for a 7 Fr dedicated plastic stent in endoscopic ultrasound-guided hepaticogastrostomy
Authors: Yuki Ishikawa-Kakiya, Hirotsugu Maruyama, Masafumi Yamamura, Kojiro Tanoue, Akira Higashimori, Shusei Fukunaga, Yasuhiro Fujiwara
Journal: Endoscopy (2023)

Endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) is expected to become widespread in the future [1]. A 7 Fr dedicated plastic stent (Through and Pass, TYPE‐IT; Gadelius Medical Co. Ltd., Tokyo, Japan) ([Fig. 1]) is often used to prevent serious adverse events, such as migration or obstruction of bile duct branches [2] [3]. However, this stent has a pigtail structure on the stomach side, making it difficult to place a guidewire through the stent. Furthermore, inserting a guidewire into the side of the stent is associated with strong frictional resistance and may result in placement intraperitoneally. When removing the stent with grasping forceps, the tube may be left in the liver as it is readily fractured ([Fig. 2]). This case demonstrates a method we devised for inserting a guidewire into a dedicated plastic stent for easy removal.
Successful retrieval of a fractured migrated pancreatic stent using an endoscopic tapered sheath for severe pancreatic duct stenosis
Authors: Akira Higashimori, Hirotsugu Maruyama, Natsumi Maeda, Yuki Ishikawa-Kakiya, Masafumi Yamamura, Kojiro Tanoue, Yasuhiro Fujiwara
Journal: Endoscopy (2023)

Endoscopic pancreatic stenting is a well-accepted treatment for symptomatic pancreatic duct stenosis [1] [2]; however, during stent removal, stent fracture can occur owing to severe pancreatic duct stenosis [3] [4]. In such cases, removal of the migrated fractured stents is difficult using conventional devices, which are unable to pass the site of the severe stenosis over the guidewire. Therefore, we used an endoscopic tapered sheath (EndoSheather; Piolax Inc., Kanagawa, Japan), a device that simultaneously enables both stenosis breakthrough and retrieval of the migrated stent (up to a diameter of 1.9 mm) through the indwelling outer sheath ([Fig. 1]).
Transgastrostomy retrograde endoscopic submucosal dissection of esophageal squamous cell carcinoma
Authors: Julia Mayumi Gregorio, Deborah Marques Centeno, Rafael Utimura Sueta, Pastor Joaquin Ortiz Mendieta, João Guilherme Ribeiro Jordão Sasso, Bruno Costa Martins, Fauze Maluf-Filho
Journal: Endoscopy (2023)

Patients undergoing treatment for laryngeal cancer are often treated with total laryngectomy, with about 11 % of patients developing a postoperative stricture [1]. Patients with head and neck tumors also develop esophageal squamous cell carcinoma (ESCC) in 5 %–10 % of cases [2]. Endoscopic submucosal dissection (ESD) is indicated for the treatment of early ESCC; however, transoral ESD is not possible in patients with recalcitrant pharyngoesophageal stricture [3]. In this case report, we demonstrate an alternative strategy for this situation.
Obtaining a free vertical margin is challenging in endoscopic submucosal dissection of a rectal neuroendocrine tumor: use of adaptive traction to improve exposure in a child
Authors: Timothée Wallenhorst, Louis-Jean Masgnaux, Jean Grimaldi, Romain Legros, Jérôme Rivory, Jérémie Jacques, Mathieu Pioche
Journal: Endoscopy (2023)

Both European Society of Gastrointestinal Endoscopy (ESGE) and American guidelines suggest resection of small rectal neuroendocrine tumors (NETs) by endoscopic submucosal dissection (ESD) for lesions up to 20 mm [1] [2]. A completely resected rectal NET (R0) with no pejorative factors for recurrence (< 10 mm, T1, grade 1, no lymphovascular invasion) requires no additional exploration and no follow-up [3].
Traction and resection in treating gastric submucosal tumor growing extraluminally by using two snares like a ropeway
Authors: Lei Gu, Yu Wu, Xiaowei Liu
Journal: Endoscopy (2023)

A 53-year-old woman with upper abdominal pain underwent computed tomography, which showed a lump with an extraluminal growth pattern located at the junction of the gastric body and antrum ([Fig. 1]). Endoscopic full-thickness resection (EFTR) is a feasible approach for gastric submucosal tumor growing extraluminally [1].
Simple extraction method using a nontraumatic tube for impacted stool in a diverticulum near the ulcer floor after endoscopic submucosal dissection
Authors: Yohei Koyama, Masakatsu Fukuzawa, Fumito Yamanishi, Taisuke Matsumoto, Hayato Yamaguchi, Takashi Kawai, Takao Itoi
Journal: Endoscopy (2023)

With the development of specific knives and traction devices, endoscopic submucosal dissection (ESD) of colorectal tumors such as those that extend into diverticula, which are technically difficult, is becoming possible [1] [2] [3] [4]. A colonic diverticulum is a false diverticulum without a muscular layer, and therefore only the serosa remains after submucosal dissection. To prevent delayed perforation, complete closure of the diverticulum is necessary; however, colonic diverticula often exist in multiples close to each other, and closure of a diverticulum containing impacted stool carries a risk of causing diverticulitis.
Successful hemostasis and subsequent cannulation using a self-assembling peptide hydrogel for bleeding after precut sphincterotomy
Authors: Tadahisa Inoue, Mayu Ibusuki, Rena Kitano, Yuji Kobayashi, Kiyoaki Ito, Masashi Yoneda
Journal: Endoscopy (2023)

Precut techniques, such as needle-knife sphincterotomy and transpancreatic sphincterotomy, are useful as salvage techniques for cases in which biliary cannulation is difficult [1]. If massive bleeding occurs during precutting, various methods may be used to achieve hemostasis, including epinephrine injection, thermal cautery, and clipping. However, all of the above may affect the duodenal papilla, complicating subsequent cannulation. Additionally, the coagulum and hematoma resulting from such an event obscure the papilla, which also impedes cannulation. A novel, self-assembling peptide hydrogel (PuraStat; 3-D Matrix, Tokyo, Japan) was recently developed as a hemostatic agent [2] [3] [4]. We present a case in which this hydrogel was useful for hemostasis and subsequent cannulation following massive bleeding during precut sphincterotomy.
Linked color imaging aids in identification of multiple rectal neuroendocrine tumors
Authors: Dmitrii Dolgunov, Ker Kan Tan, Bernice Tan, Calvin Jianyi Koh, Chieh Sian Koo
Journal: Endoscopy (2023)

A 63-year-old man with a history of three synchronous primary cancers (colon, lung, and thyroid) underwent surveillance colonoscopy after his curative left hemicolectomy. A new 8 mm rectal lesion was identified and removed with hot snare polypectomy. Histology showed a grade 1 rectal neuroendocrine tumor (NET). Repeat colonoscopy 6 months later showed five new sub-centimeter rectal NETs, which were removed with cap-assisted endoscopic mucosal resection (EMR).
Successful resection of a cavernous hemangioma involving the rectal muscularis propria layer by endoscopic full-thickness resection
Authors: Wei Liu, Yinong Zhu, Xianglei Yuan, Bing Hu
Journal: Endoscopy (2023)

A 46-year-old woman with a history of hematochezia visited our institution for colonoscopy. A globular submucosal tumor with a diameter of approximately 20 mm and mucosal hyperemia was detected in the rectum ([Fig. 1 a]). Further endoscopic ultrasonography showed a well-defined, homogeneous, hyperechoic mass 18 mm × 9 mm in size originating from the submucosal layer ([Fig. 1 b]), suggesting that the mass might be a hemangioma. At this point, endoscopic submucosal dissection (ESD) was considered for the treatment of the lesion. First, after submucosal injection we made a circumferential mucosal incision using a dual knife (Olympus, Tokyo, Japan). However, during the procedure we found that the boundary between the lesion and the muscularis propria layer was not clear ([Fig. 1 c]). Therefore, ESD was not the right choice to ensure en bloc resection of the lesion, and endoscopic full-thickness resection (EFTR) was believed to be a better option for this patient ([Fig. 1 d], [Fig. 2 a], [Video 1]). After partial dissection of the lesion, we used a snare to complete EFTR of the lesion, and finally the defect was successfully closed using titanium clips and a nylon cord (Micro-Tech, Nanjing, China) ([Fig. 1 e]). Histopathology revealed a cavernous hemangioma with involvement of the muscularis propria layer ([Fig. 2 b]). The patient was discharged 3 days after treatment without any complications. A follow-up colonoscopy was performed 3 months later and indicated that the defect was basically healed ([Fig. 1 f]).
One-step balloon-assisted direct peroral cholangioscopy prior to placing the anti-reflux self-expandable metal stent
Authors: Seiji Fujigaki, Tsuyoshi Sanuki, Akira Shirohata, Ryusuke Ariyoshi, Katsuhide Tanaka, Teruhisa Morikawa, Yoshikazu Kinoshita
Journal: Endoscopy (2023)

Endoscopic biliary drainage with a self-expandable metal stent (SEMS) is the standard treatment for malignant biliary obstructions. Duodenobiliary reflux, which is an unavoidable concern after SEMS placement, results in stent dysfunction [1]. The usefulness of a duckbill-type anti-reflux self-expandable metal stent (D-ARMS) for recurrent biliary obstruction (RBO) has been reported [2].
Pulmonary endothelium-targeted nanoassembly of indomethacin and superoxide dismutase relieves lung inflammation
Authors: Yi Yang, Makhloufi Zoulikha, Qingqing Xiao, Feifei Huang, Qi Jiang, Xiaotong Li, Zhenfeng Wu, Wei He
Journal: Acta Pharmaceutica Sinica B (2023)

Lung inflammation is an essential inducer of various diseases and is closely related to pulmonary-endothelium dysfunction. Herein, we propose a pulmonary endothelium-targeted codelivery system of anti-inflammatory indomethacin (IND) and antioxidant superoxide dismutase (SOD) by assembling the biopharmaceutical SOD onto the “vector” of rod-like pure IND crystals, followed by coating with anti-ICAM-1 antibody (Ab) for targeting endothelial cells. The codelivery system has a 237 nm diameter in length and extremely high drug loading of 39% IND and 2.3% SOD. Pharmacokinetics and biodistribution studies demonstrate the extended blood circulation and the strong pulmonary accumulation of the system after intravenous injection in the lipopolysaccharide (LPS)-induced inflammatory murine model. Particularly, the system allows a robust capacity to target pulmonary endothelium mostly due to the rod-shape and Ab coating effect. In vitro, the preparation shows the synergistic anti-inflammatory and antioxidant effects in LPS-activated endothelial cells. In vivo, the preparation exhibits superior pharmacodynamic efficacy revealed by significantly downregulating the inflammatory/oxidative stress markers, such as TNF-α, IL-6, COX-2, and reactive oxygen species (ROS), in the lungs. In conclusion, the codelivery system based on rod-like pure crystals could well target the pulmonary endothelium and effectively alleviate lung inflammation. The study offers a promising approach to combat pulmonary endothelium-associated diseases.
UBTF tandem duplications are rare but recurrent alterations in adult AML and associated with younger age, myelodysplasia, and inferior outcome
Authors: Julia-Annabell Georgi, Sebastian Stasik, Jan-Niklas Eckardt, Sven Zukunft, Marita Hartwig, Christoph Röllig, Jan Moritz Middeke, Uta Oelschlägel, Utz Krug, Tim Sauer, Sebastian Scholl, Andreas Hochhaus, Tim H. Brümmendorf, Ralph Naumann, Björn Steffen, Hermann Einsele, Markus Schaich, Andreas Burchert, Andreas Neubauer, Kerstin Schäfer-Eckart, Christoph Schliemann, Stefan W. Krause, Mathias Hänel, Richard Noppeney, Ulrich Kaiser, Claudia D. Baldus, Martin Kaufmann, Carsten Müller-Tidow, Uwe Platzbecker, Wolfgang E. Berdel, Hubert Serve, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig, Frank Kroschinsky, Christian Thiede
Journal: Blood Cancer Journal (2023)

Abstract Tandem-duplication mutations of the UBTF gene ( UBTF -TDs) coding for the upstream binding transcription factor have recently been described in pediatric patients with acute myeloid leukemia (AML) and were found to be associated with particular genetics (trisomy 8 (+8), FLT3 -internal tandem duplications ( FLT3 -ITD), WT1 -mutations) and inferior outcome. Due to limited knowledge on UBTF- TDs in adult AML, we screened 4247 newly diagnosed adult AML and higher-risk myelodysplastic syndrome (MDS) patients using high-resolution fragment analysis. UBTF -TDs were overall rare ( n = 52/4247; 1.2%), but significantly enriched in younger patients (median age 41 years) and associated with MDS-related morphology as well as significantly lower hemoglobin and platelet levels. Patients with UBTF -TDs had significantly higher rates of +8 (34% vs. 9%), WT1 (52% vs. 7%) and FLT3 -ITD (50% vs. 20.8%) co-mutations, whereas UBTF -TDs were mutually exclusive with several class-defining lesions such as mutant NPM1 , in-frame CEBPA bZIP mutations as well as t(8;21). Based on the high-variant allele frequency found and the fact that all relapsed patients analyzed ( n = 5) retained the UBTF -TD mutation, UBTF -TDs represent early clonal events and are stable over the disease course. In univariate analysis, UBTF -TDs did not represent a significant factor for overall or relapse-free survival in the entire cohort. However, in patients under 50 years of age, who represent the majority of UBTF -mutant patients, UBTF -TDs were an independent prognostic factor for inferior event-free (EFS), relapse-free (RFS) and overall survival (OS), which was confirmed by multivariable analyses including established risk factors such as age and ELN2022 genetic risk groups (EFS [HR: 2.20; 95% CI 1.52–3.17, p &lt; 0.001], RFS [HR: 1.59; 95% CI 1.02–2.46, p = 0.039] and OS [HR: 1.64; 95% CI 1.08–2.49, p = 0.020]). In summary, UBTF -TDs appear to represent a novel class-defining lesion not only in pediatric AML but also younger adults and are associated with myelodysplasia and inferior outcome in these patients.
Sex-specific assumptions and their importance in models of sexual selection
Authors: Charlotte de Vries, Jussi Lehtonen
Journal: Trends in Ecology & Evolution (2023)

Sexual selection is a field coloured by tension and contrasting views. One contested claim is the causal link from the definition of the sexes (anisogamy) to divergent selection on the sexes. Does theory truly engage with this claim? We survey the extent to which theory makes sex-specific assumptions and engages with anisogamy, and discuss these issues in a broader context. The majority of theory in sexual selection makes sex-specific assumptions and does not engage with the definition of the sexes. While this does not invalidate existing results, debates and criticisms regarding sexual selection force us to think deeper about its logical foundations. We discuss ways to strengthen the foundations of sexual selection theory by relaxing central assumptions.
Versatile flexible micelles integrating mucosal penetration and intestinal targeting for effectively oral delivery of paclitaxel
Authors: Chao Liu, Wei Liu, Yanhong Liu, Hongxia Duan, Liqing Chen, Xintong Zhang, Mingji Jin, Minhu Cui, Xiuquan Quan, Libin Pan, Jiachun Hu, Zhonggao Gao, Yan Wang, Wei Huang
Journal: Acta Pharmaceutica Sinica B (2023)

The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.
A non-transmissible live attenuated SARS-CoV-2 vaccine
Authors: Julia M. Adler, Ricardo Martin Vidal, Anne Voß, Sandra Kunder, Mariana Nascimento, Azza Abdelgawad, Christine Langner, Daria Vladimirova, Nikolaus Osterrieder, Achim D. Gruber, Dusan Kunec, Jakob Trimpert
Journal: Molecular Therapy (2023)

Live attenuated vaccines (LAVs) administered via the mucosal route may offer better control of the COVID-19 pandemic than non-replicating vaccines injected intramuscularly. Conceptionally, LAVs have several advantages, including presentation of the entire antigenic repertoire of the virus, and the induction of strong mucosal immunity. Thus, immunity induced by LAV could offer superior protection against future surges of COVID-19 cases caused by emerging SARS-CoV-2 variants. However, LAVs carry the risk of unintentional transmission. To address this issue, we investigated whether transmission of a SARS-CoV-2 LAV candidate can be blocked by removing the furin cleavage site (FCS) from the spike protein. The level of protection and immunity induced by the attenuated virus with the intact FCS was virtually identical to the one induced by the attenuated virus lacking the FCS. Most importantly, removal of the FCS completely abolished horizontal transmission of vaccine virus between cohoused hamsters. Furthermore, the vaccine was safe in immunosuppressed animals and showed no tendency to recombine in vitro or in vivo with a SARS-CoV-2 field strain. These results indicate that removal of the FCS from SARS-CoV-2 LAV is a promising strategy to increase vaccine safety and prevent vaccine transmission without compromising vaccine efficacy. Live attenuated vaccines (LAVs) administered via the mucosal route may offer better control of the COVID-19 pandemic than non-replicating vaccines injected intramuscularly. Conceptionally, LAVs have several advantages, including presentation of the entire antigenic repertoire of the virus, and the induction of strong mucosal immunity. Thus, immunity induced by LAV could offer superior protection against future surges of COVID-19 cases caused by emerging SARS-CoV-2 variants. However, LAVs carry the risk of unintentional transmission. To address this issue, we investigated whether transmission of a SARS-CoV-2 LAV candidate can be blocked by removing the furin cleavage site (FCS) from the spike protein. The level of protection and immunity induced by the attenuated virus with the intact FCS was virtually identical to the one induced by the attenuated virus lacking the FCS. Most importantly, removal of the FCS completely abolished horizontal transmission of vaccine virus between cohoused hamsters. Furthermore, the vaccine was safe in immunosuppressed animals and showed no tendency to recombine in vitro or in vivo with a SARS-CoV-2 field strain. These results indicate that removal of the FCS from SARS-CoV-2 LAV is a promising strategy to increase vaccine safety and prevent vaccine transmission without compromising vaccine efficacy.